Alterations in excitability and cell-to-cell communication may play a significant role in the development of ventricular conduction block processes and rhythm disturbances. A multidisciplinary approach will be used to investigate the electrophysiological bases of cardiac impulse propagation, in an attempt to develop accurate models for the study of these alterations. We will utilize isolated heart tissue preparations, mathematical simulations and supercomputer technology to pursue our two major specific aims: I. We will study the role of intercellular coupling, excitability and active membrane properties in two-dimensional anisotropic propagation in isolated sheep venticular epicardium and in computer simulations utilizing large one-, two- and three-dimensional arrays of electrically coupled heart cells. In our ventricular muscle preparations, we will use computer-aided multiple electrode mapping and premature stimulation techniques to study conduction velocity/Vmax relationships and discontinuities in anisotropic propagation induced by changes in electrical coupling and/or excitability. The results of these studies will be compared with those of simulations in which equivalent changes in coupling and excitability will be modelled. In addition, a perfusable suction electrode technique for transmembrane current application will be used in these experiments to determine directional differences in intercellular communication. Moreover, we will make use also of specific pharmacologic tools and of computer modelling to investigate the roles of electrical coupling and fiber orientation in anisotropic cardiac impulse propagation. II. We will investigate the cellular mechanisms of rate-dependent block processes in biological and numerical models of non-homogeneous cardiac Purkinje fibers and ventricular muscle. We will determine the effects of segmental changes in excitability, membrane resistance and intercellular resistance on input-output characteristics, refractory period and propagation velocity across junctional areas between normal and depressed tissues. Finally, we will apply chaos theory to elucidate the quantitative basis of cyclic patterns of conduction impairment, and the conditions leading to period doubling and irregular dynamics of excitation and impulse propagation in cardiac tissues. Systematic integration of experimental and modelling studies should ensure the achievement of our long-term objective: to provide accurate background for determining precisely the mechanisms of cardiac impulse propagation and its alterations.